ABSTRACT
Owing to a strong photothermal response in the near-IR spectral range and very low toxicity, titanium nitride (TiN) nanoparticles (NPs) synthesized by pulsed laser ablation in liquids (PLAL) present a novel appealing object for photo-induced therapy of cancer, but the properties of these NPs still require detailed investigation. Here, we have elaborated methods of femtosecond laser ablation from the TiN target in a variety of liquid solutions, including acetonitrile, dimethylformamide, acetone, water, and H2O2, to synthesize TiN NPs and clarify the effect of liquid type on the composition and properties of the formed NPs. The ablation in all solvents led to the formation of spherical NPs with a mean size depending on the liquid type, while the composition of the NPs ranged from partly oxidized TiN to almost pure TiO2, which conditioned variations of plasmonic peak in the region of relative tissue transparency (670-700 nm). The degree of NP oxidation depended on the solvent, with much stronger oxidation for NPs prepared in aqueous solutions (especially in H2O2), while the ablation in organic solvents resulted in a partial formation of titanium carbides as by-products. The obtained results contribute to better understanding of the processes in reactive PLAL and can be used to design TiN NPs with desired properties for biomedical applications.
ABSTRACT
Having plasmonic absorption within the biological transparency window, titanium nitride (TiN) nanoparticles (NPs) can potentially outperform gold counterparts in phototheranostic applications, but characteristics of available TiN NPs are still far from required parameters. Recently emerged laser-ablative synthesis opens up opportunities to match these parameters as it makes possible the production of ultrapure low size-dispersed spherical TiN NPs, capable of generating a strong phototherapy effect under 750-800 nm excitation. This study presents the first assessment of toxicity, biodistribution and pharmacokinetics of laser-synthesized TiN NPs. Tests in vitro using 8 cell lines from different tissues evidenced safety of both as-synthesized and PEG-coated NPs (TiN-PEG NPs). After systemic administration in mice, they mainly accumulated in liver and spleen, but did not cause any sign of toxicity or organ damage up to concentration of 6 mg kg-1, which was confirmed by the invariability of blood biochemical parameters, weight and hemotoxicity examination. The NPs demonstrated efficient passive accumulation in EMT6/P mammary tumor, while concentration of TiN-PEG NPs was 2.2-fold higher due to "stealth" effect yielding 7-times longer circulation in blood. The obtained results evidence high safety of laser-synthesized TiN NPs for biological systems, which promises a major advancement of phototheranostic modalities on their basis.
